Genetic, molecular and clinical studies have lead to the identification of a medical disorder called juvenile hemochromatosis (sometimes called “JH” or “juvenile haemochromatosis”), which is also known as hemochromatosis type 2 (“HFE2”).
In some families juvenile hemochromatosis shows linkage to chromosome 1q21, whereas in others it is caused by mutation in the gene encoding hepcidin antimicrobial peptide, which maps to chromosome 19q13. The two forms of juvenile hemochromatosis (HFE2) are tentatively designated HFE2A and HFE2B, respectively. The present invention relates to HFE2A gene and protein, (the JH gene linked to chromosome Iq21), and more specifically to the cleavage products of HFE2A.
The intact (i.e. full-length) HFE2A has been implicated in diseases of iron metabolism (PCT Patent Publication No. WO 04/092405). Specific fragments of HFE2A, i.e., cleavage products, have not, previously, been explicitly identified and the role they may play in the regulation of diseases of iron metabolism has remained obscured.
Such fragments are a soluble form of HFE2A and the present invention for the first time offers these as a critical regulator of iron metabolism. Thus, an object of the present invention is to provide cleavage products of the HFE2A, thereby facilitating development of more potent agents for treating and diagnosing iron overload diseases and iron deficiency diseases. Moreover, such identification enables a better understanding of the operation of the HFE2A and its cleavage products in the development and regulation of diseases of iron metabolism, in general, and all forms of iron overload in particular hemochromatosis, as well as Anemia of Inflammation, in particular.